- A base labile handle for solid phase organic chemistry
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Several arylsulfonamides have been synthesised on solid phase using a new base labile handle. Cleavage front the solid support is accomplished by oxidation of the sulfide to the sulfone, followed by β-elimination in base media.
- Garcia-Echeverria, Carlos
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- Structure-activity relationships of agonists for the orphan G protein-coupled receptor GPR27
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GPR27 belongs, with GPR85 and GPR173, to a small subfamily of three receptors called “Super-Conserved Receptors Expressed in the Brain” (SREB). It has been postulated to participate in key physiological processes such as neuronal plasticity, energy metabolism, and pancreatic β-cell insulin secretion and regulation. Recently, we reported the first selective GPR27 agonist, 2,4-dichloro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (I, pEC50 6.34, Emax 100%). Here, we describe the synthesis and structure-activity relationships of a series of new derivatives and analogs of I. All products were evaluated for their ability to activate GPR27 in an arrestin recruitment assay. As a result, agonists were identified with a broad range of efficacies including partial and full agonists, showing higher efficacies than the lead compound I. The most potent agonist was 4-chloro-2,5-difluoro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7y, pEC50 6.85, Emax 37%), and the agonists with higher efficacies were 4-chloro-2-methyl-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7p, pEC50 6.04, Emax 123%), and 2-bromo-4-chloro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7r, pEC50 5.99, Emax 123%). Docking studies predicted the putative binding site and interactions of agonist 7p with GPR27. Selected potent agonists were found to be soluble and devoid of cellular toxicity within the range of their pharmacological activity. Therefore, they represent important new tools to further characterize the (patho)physiological roles of GPR27.
- Blavier, Jeremy,Charles, Ma?lle,Hanson, Julien,Kronenberger, Thales,Laschet, Céline,Müller, Christa E.,Pillaiyar, Thanigaimalai,Rosato, Francesca,Wozniak, Monika
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- Synthesis, Computational Docking, and Antimycobacterial Study of Novel N'-phenyl-4-pyrrol-1-yl-benzenesulfonamide Derivatives
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Fresh sequences of pyrrole linked N'-phenyl-4-pyrrolyl-benzenesulfonamide derivatives were synthesized by different synthetic methods. Synthesis of the N'-phenyl-4-(1H-pyrrol-1-yl) benzenesulfonamides 5(a-e)/4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-phenylbenzenesulfonamides 6(a-e) was achieved by refluxing 2,5-dimethoxytetrahydrofuran/hexane 2,5-dione separately in presence of acetic acid. Further, synthesis of N-(4-(N'-phenylsulfamoyl)phenyl)-4-(1H-pyrrol-1-yl)benzamides 8(a-b)/4-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(4-(N'-phenylsulfamoyl)phenyl)benzamides 10(a-b) was achieved by cold stirring of 4-(1H-pyrrol-1-yl)benzoic acid (7)/2,5-dimethyl-1H-pyrrol-1-yl)benzoic acid (9) correspondingly in the presence of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate, N', N'-diisopropylethylamine, and Dimethylformamide. In vitro anti-tubercular study of afresh compounds has shown good minimum inhibitory concentration values (0.4-12.5 μg/mL) counter to Mycobacterium tuberculosis H37Rv, while the corresponding study of reported molecules for antibacterial activity disclosed considerable inhibition values (0.4-25 μg/mL) counter to Escherichia coli (Gram-ve) than Staphylococcus aureus (Gram +ve).
- Alqahtani, Yahya S.,Joshi, Shrinivas D.,Kumar, S. R. Prem,Pavitra, H.
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p. 405 - 416
(2021/11/22)
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- Discovery of secondary sulphonamides as IDO1 inhibitors with potent antitumour effects in vivo
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Indoleamine 2,3-dioxygenase 1 (IDO1) as a key rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism plays an important role in tumour immune escape. Herein, a variety of secondary sulphonamides were synthesised and evaluated in the HeLa cell-based IDO1/kynurenine assay, leading to the identification of new IDO1 inhibitors. Among them, compounds 5d, 5l and 8g exhibited the strongest inhibitory effect with significantly improved activity over the hit compound BS-1. The in vitro results showed that these compounds could restore the T cell proliferation and inhibit the differentiation of na?ve CD4+ T cell into highly immunosuppressive FoxP3+ regulatory T (Treg) cell without affecting the viability of HeLa cells and the expression of IDO1 protein. Importantly, the pharmacodynamic assay showed that compound 5d possessed potent antitumour effect in both CT26 and B16F1 tumours bearing immunocompetent mice but not in immunodeficient mice. Functionally, subsequent experiments demonstrated that compound 5d could effectively inhibit tumour cell proliferation, induce apoptosis, up-regulate the expression of IFN-γ and granzyme B, and suppress FoxP3+ Treg cell differentiation, thereby activate the immune system. Thus, compound 5d could be a potential and efficacious agent for further evaluation.
- Ge, Shushan,Guo, Wenjie,Hu, Yue,Lai, Yisheng,Li, Yuezhen,Liu, Wen,Ma, Xuewei,Wang, Fang,Wang, Yan,Xu, Qiang,Zheng, Yingbo,Zhong, Haiqing,Zou, Yi
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p. 1240 - 1257
(2020/06/18)
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- Effect of photodynamic antibacterial chemotherapy combined with antibiotics on Gram-positive and gram-negative bacteria
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The well-known and rapidly growing phenomenon of bacterial resistance to antibiotics is caused by uncontrolled, excessive and inappropriate use of antibiotics. One of alternatives to antibiotics is Photodynamic Antibacterial Chemotherapy (PACT). In the present study, the effect of PACT using a photosensitizer Rose Bengal alone and in combination with antibiotics including methicillin and derivatives of sulfanilamide synthesized by us was tested against antibiotic-sensitive and antibiotic-resistant clinical isolates of Gram-positive S. aureus and Gram-negative P. aeruginosa. Antibiotic-sensitive and resistant strains of P. aeruginosa were eradicated by Rose Bengal under illumination and by sulfanilamide but were not inhibited by new sulfanilamide derivatives. No increase in sensitivity of P. aeruginosa cells to sulfanilamide was observed upon a combination of Rose Bengal and sulfanilamide under illumination. All tested S. aureus strains (MSSA and MRSA) were effectively inhibited by PACT. When treated with sub-MIC concentrations of Rose Bengal under illumination, the minimum inhibitory concentrations (MIC) of methicillin decreased significantly for MSSA and MRSA strains. In some cases, antibiotic sensitivity of resistant strains can be restored by combining antibiotics with PACT.
- Ilizirov, Yana,Formanovsky, Andrei,Mikhura, Irina,Paitan, Yossi,Nakonechny, Faina,Nisnevitch, Marina
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- ADENINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
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The present invention relates to a compound suitable for use as a kinase inhibitor according to general formula (I) [compound (C), herein after], or the N- oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof, formula (I) wherein A, R1, R2, R3, R3', R4, R4', X, Y, Z, T are as defined in the claims. The invention further relates to an in vitro method of inhibiting protein kinase activity which comprises contacting a protein kinase with a compound of formula (I), or the N-oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof. The invention further relates to the compounds of formula (I) per se, as well as to their use as a medicament, and for use or in a method of treatment of a disease mediated by a protein kinase selected from cancer, inflammatory disorders, cardiovascular diseases, viral induced diseases, circulatory diseases, fibro-proliferative diseases and pain sensitization disorders.
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- Cyclometalated palladium pre-catalyst for N-alkylation of amines using alcohols and regioselective alkylation of sulfanilamide using aryl alcohols
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Simple pyrazole based palladacycle-phosphine with a high turnover has been developed and applied for the N-alkylation of amines and sulfanilamide using alcohols as substrates by hydrogen borrowing strategy. N-alkylation of primary and secondary amines resulted in high isolated yields at 100–130 °C, under solvent free conditions. More challenging secondary aliphatic as well as aromatic alcohols were also successfully utilized as alkylating agents under similar reaction conditions. The turn over number reached up to 43000 for N-benzylation of aniline using benzyl alcohol. Notably, regioselective N-alkylation of 2-aminobenzothiazole and 4-aminobenzenesulfonamide to the corresponding 2-N-(alkylamino)azoles and 4-amino-(N-alkyl)benzenesulfonamides using alcohols as alkylating agents have been achieved using our new pre-catalyst-phosphine system.
- Mamidala, Ramesh,Mukundam, Vanga,Dhanunjayarao, Kunchala,Venkatasubbaiah, Krishnan
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supporting information
p. 2225 - 2233
(2017/03/24)
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- Synthesis process of sulfonamide compounds in microwave system
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The invention discloses a synthesis process of sulfonamide compounds in a microwave system. The synthesis process is realized by the following steps: by using CuCl as a catalyst and FeCl3 as an oxidant, carrying out carbon-hydrogen activating and carbon-nitrogen coupling reaction in a DMF (Dimethyl Formamide) by substituting sulfanilamide and methylbenzene through microwave heating and efficient catalysis for 10 to 60 minutes; extracting a product by using ethyl acetate; carrying out vacuum concentration; carrying out column chromatographic purification on a product to obtain the sulfonamide compounds. The synthesis process is a method for efficiently preparing the sulfonamide compounds, which is environment-friendly and is simple and convenient to operate. Compared with the prior art, the synthetic process disclosed by the invention has the advantages of remarkably-increased reaction speed compared with that under a conventional heating condition, mild reaction conditions, simple operation, high yield, safety, low cost and environmental protection.
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Paragraph 0007; 0021; 0037
(2017/08/14)
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- Potent and selective N-(4-sulfamoylphenyl)thiourea-based GPR55 agonists
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To date, many known G protein-coupled receptor 55 (GPR55) ligands are those identified among the cannabinoids. In order to further study the function of GPR55, new potent and selective ligands are needed. In this study, we utilized the screening results from PubChem bioassay AID 1961 which reports the results of Image-based HTS for Selective Agonists of GPR55. Three compounds, CID1792579, CID1252842 and CID1011163, were further evaluated and used as a starting point to create a series of nanomolar potency GPR55 agonists with N-(4-sulfamoylphenyl)thiourea scaffold. The GPR55 activity of the compounds were screened by using a commercial β-arrestin PathHunter assay and the potential compounds were further evaluated by using a recombinant HEK cell line exhibiting GPR55-mediated effects on calcium signalling. The designed compounds were not active when tested against various endocannabinoid targets (CB1R, CB2R, FAAH, MGL, ABHD6 and ABHD12), indicating compounds' selectivity for the GPR55. Finally, structure-activity relationships of these compounds were explored.
- Yrj?l?, Sari,Parkkari, Teija,Navia-Paldanius, Dina,Laitinen, Tuomo,Kaczor, Agnieszka A.,Kokkola, Tarja,Adusei-Mensah, Frank,Savinainen, Juha R.,Laitinen, Jarmo T.,Poso, Antti,Alexander, Amy,Penman, June,Stott, Lisa,Anskat, Marie,Irving, Andrew J.,Nevalainen, Tapio J.
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p. 119 - 132
(2015/11/24)
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- Amino-(N-alkyl) benzsulfamide synthesis method
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The invention discloses an amino-(N-alkyl) benzsulfamide synthesis method. The method comprises the steps of adding aminobenzenesul fonamide, an iridium complex catalyst, alkali, compound alcohol and the solvent tert-amyl alcohol into a reaction container for reaction lasting several hours at 120-150 DEG C, then reducing temperature to room temperature, conducting rotary evaporation to remove the solvent, and then conducting column separation to obtain the target compound. Commercial aminobenzenesul fonamide and nearly non-toxic compound alcohol are used as starting materials, only water is generated as reaction byproduct, and no environment harm is done; reaction atom economy is high.
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Paragraph 0021-0024
(2017/04/14)
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- Effective Recognition of Different Types of Amino Groups: From Aminobenzenesulfonamides to Amino-(N-alkyl)benzenesulfonamides via Iridium-Catalyzed N-Alkylation with Alcohols
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(Chemical Equation Presented). A simple, highly efficient, and general strategy for the direct synthesis of amino-(N-alkyl)benzenesulfonamides has been accomplished via direct N-alkylation of aminobenzenesulfonamides bearing both different types of amino groups with alcohols as alkylating agents. Notably, this research exhibited the potential for the recognition of different types of amino groups in the N-alkylation of complex molecules with alcohols, facilitating the progress of the transition-metal-catalyzed "hydrogen autotransfer (or hydrogen-borrowing) process."
- Lu, Lei,Ma, Juan,Qu, Panpan,Li, Feng
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supporting information
p. 2350 - 2353
(2015/06/02)
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- A highly active bifunctional iridium complex with an alcohol/alkoxide- tethered N-heterocyclic carbene for alkylation of amines with alcohols
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A series of new iridium(III) complexes containing bidentate N-heterocyclic carbenes (NHC) functionalized with an alcohol or ether group (NHC-OR, R=H, Me) were prepared. The complexes catalyzed the alkylation of anilines with alcohols as latent electrophiles. In particular, biscationic IrIII complexes of the type [Cp*(NHC-OH)Ir(MeCN)]2+2[BF4 -] afforded higher-order amine products with very high efficiency; up to >99 % yield using a 1:1 ratio of reactants and 1-2.5 mol % of Ir, in short reaction times (2-16 h) and under base-free conditions. Quantitative yields were also obtained at 50 °C, although longer reaction times (48-60 h) were needed. A large variety of aromatic amines have been alkylated with primary and secondary alcohols. The reactivity of structurally related iridium(III) complexes was also compared to obtain insights into the mechanism and into the structure of possible catalytic intermediates. The IrIII complexes were stable towards oxygen and moisture, and were characterized by NMR, HRMS, single-crystal X-ray diffraction, and elemental analyses. Copyright
- Bartoszewicz, Agnieszka,Marcos, Rocio,Sahoo, Suman,Inge, A. Ken,Zou, Xiaodong,Martin-Matute, Belen
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supporting information
p. 14510 - 14519
(2013/01/15)
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- Acyl derivatives of p-aminosulfonamides and dapsone as new inhibitors of the arginine methyltransferase hPRMT1
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Arginine methylation is an epigenetic modification that receives increasing interest as it plays an important role in several diseases. This is especially true for hormone-dependent cancer, seeing that histone methylation by arginine methyltransferase I (PRMT1) is involved in the activation of sexual hormone receptors. Therefore, PRMT inhibitors are potential drugs and interesting tools for cell biology. A dapsone derivative called allantodapsone previously identified by our group served as a lead structure for inhibitor synthesis. Acylated derivatives of p-aminobenzenesulfonamides and the antilepra drug dapsone were identified as new inhibitors of PRMT1 by in vitro testing. The bis-chloroacetyl amide of dapsone selectively inhibited human PRMT1 in the low micromolar region and was selective for PRMT1 as compared to the arginine methyltransferase CARM1 and the lysine methyltransferase Set7/9. It showed anticancer activity on MCF7a and LNCaP cells and blocked androgen dependent transcription specifically in a reporter gene system. Likewise, a transcriptional block was also demonstrated in LNCaP cells using quantitative RT-PCR on the mRNA of androgen dependent genes.
- Bissinger, Elisabeth-Maria,Heinke, Ralf,Spannhoff, Astrid,Eberlin, Adrien,Metzger, Eric,Cura, Vincent,Hassenboehler, Pierre,Cavarelli, Jean,Schuele, Roland,Bedford, Mark T.,Sippl, Wolfgang,Jung, Manfred
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p. 3717 - 3731
(2011/08/03)
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- Pyridazine derivatives and related compounds, part 28.1 pyridazinesulfonamides: Synthesis and antimicrobial activity
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The reaction of 3-chloropyridazine 1 with N -(un)Substituted 4-aminosulfonamides 3 gave the 3-substituted aminopyridazines 4. Also In addition, pyridazine-3-sulfonamides 7 were prepared from the reaction of pyridazine-3-sulfonylchloride 6 with different amines. All of these derivatives have been characterized by analytical and spectroscopic studies, and also were tested for their in vitro antibacterial and antifungal activity against a variety of microorganisms.
- El-Mariah, Fatma,Nassar, Ekhlass,Hosny, Mona,Deeb, Ali
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experimental part
p. 92 - 102
(2009/04/16)
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- Novel lead structures for antimalarial farnesyltransferase inhibitors
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Through the combination of nitrophenylfurylacryloyl moiety which has been designed to occupy an aryl binding site of farnesyltransferase with several AA(X)-peptidomimetic substructures some novel farnesyltransferase inhibitors were obtained. Evaluation of their antimalarial activity and some initial modifications yielded a 4-benzophenone- and a sulfonamid-based novel lead for antimalarial farnesyltransferase inhibitors.
- Kettler,Sakowski,Wiesner,Ortmann,Jomaa,Schlitzer, Martin
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p. 323 - 327
(2007/10/03)
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- Compounds for the treatment of protozoal diseases
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The invention relates to new diphenylurea having the formula (I) or a salt thereof, where Y is C=O, C=S, C=NH, (C=O)2 or SO2; and to processes for the preparation of these compounds and to their use in the treatment of protozoal diseases and to diseases where the inhibition of intracellular protein-degradation pathways is of benefit.
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- NOVEL ADENOSINE A3 RECEPTOR AGONISTS
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The invention realizes that a series of sulfonamido derivatives with a conserved uronamide group at the 5' position provide superior A3 receptor affinity as well as selectivity. These new adenosine agonists are sulfonamido deritatives N-substituted with aliphatic groups (cyclic or linear) or aromatic radicals.
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Page/Page column 35-36
(2008/06/13)
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- Compounds for the treatment of protozoal diseases
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The invention relates to new diphenylurea having the formula (I) or a salt thereof, where Y is C═O, C═S, C═NH, (C═O)2 or SO2; and to processes for the preparation of these compounds and to their use in the treatment of protozoal diseases and to diseases where the inhibition of intracellular protein-degradation pathways is of benefit.
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- Compounds for the treatment of protozoal diseases
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Treatment of Protozoan Infections with new diphenylurea derivatives.
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- Neuropeptide Y antagonists
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The compound is a neuropeptide Y antagonist and is effective in treating feeding disorders, cardiovascular diseases and other physiological disorders.
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Page column 38
(2010/02/05)
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